The long range goal of the proposed research is to understand the molecular basis; and physiological role(s) of the Escherichia coli and Salmonella typhimurium omega proteins (DNA topoisomerases I). The specific major objectives we plan to achieve over a 5 to 6 year period are: l. the isolation and characterization of homogeneous omega protein from Salmonella typhimurium; 2. measurement of the binding of omega proteins to circular DNA molecules as a function of the superhelical density of the substrate; 3. development of methods to distinguish between the E. coli and S. typhimurium omega proteins; 4. genetic mapping of the omega protein structural gene, and; 5. isolation and characterization of omega mutants. Among subsidiary objectives is the isolation and characterization of endonuclease deficient mutants of S. typhimurium suitable as a source of endonuclease-free omega protein.